title: [18F]FMeNER-D2: reliable fully-automated synthesis for visualization of the norepinephrine transporter.
abstract: OBJECTIVE
  In neurodegenerative diseases and neuropsychiatric disorders dysregulation of the norepinephrine transporter (NET) has been reported. For visualization of NET availability and occupancy in the human brain PET imaging can be used. Therefore, selective NET-PET tracers with high affinity are required. Amongst these, [(18)F]FMeNER-D2 is showing the best results so far. Furthermore, a reliable fully automated radiosynthesis is a prerequisite for successful application of PET-tracers. The aim of this work was the automation of [(18)F]FMeNER-D2 radiolabelling for subsequent clinical use. The presented study comprises 25 automated large-scale syntheses, which were directly applied to healthy volunteers and adult patients suffering from attention deficit hyperactivity disorder (ADHD).
  
  
  METHODS
  Synthesis of [(18)F]FMeNER-D2 was automated within a Nuclear Interface Module. Starting from 20-30 GBq [(18)F]fluoride, azeotropic drying, reaction with Br2CD2, distillation of 1-bromo-2-[(18)F]fluoromethane-D2 ([(18)F]BFM) and reaction of the pure [(18)F]BFM with unprotected precursor NER were optimized and completely automated. HPLC purification and SPE procedure were completed, formulation and sterile filtration were achieved on-line and full quality control was performed.
  
  
  RESULTS
  Purified product was obtained in a fully automated synthesis in clinical scale allowing maximum radiation safety and routine production under GMP-like manner. So far, more than 25 fully automated syntheses were successfully performed, yielding 1.0-2.5 GBq of formulated [(18)F]FMeNER-D2 with specific activities between 430 and 1707 GBq/μmol within 95 min total preparation time.
  
  
  CONCLUSIONS
  A first fully automated [(18)F]FMeNER-D2 synthesis was established, allowing routine production of this NET-PET tracer under maximum radiation safety and standardization.
authors.affiliation: Radiochemistry and Biomarker Development Unit, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria; Department of Inorganic Chemistry, University of Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Rami-Mark
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
mesh_terms: D001331:Automation; D006801:Humans; D007267:Injections; D009025:Morpholines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry / Q000379:methods*
chemical_list: C506462:2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholine; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins
keywords: Automation; FMeNER; FMeNER-D2; Fluorine-18; Norepinephrine transporter; PET; Radiosynthesis